Drug Nanopariticles By Solvent Eliminate Via The Employment Of Branched Block Copolymer Nanoparticles

A large percentage of drug compounds exhibit low water solubility and hence low bioa-vailability and therapeutic efficacy. This may be addressed by preparation of drug nanocrystals, which can give much enhanced dissolution rate and use directly for treatment. Various methods have been developed to produce drug nanocrystals,including wet milling, homogenization, solution precipitation, emulsion diffusion, and the recently developed emulsion freeze-drying. The drawback for these methods may include difficult control in particles size and use of surfactants and polymer, usually leading to low ratio of drug to stabilizer. Here, biocompatible branched block copolymer nanoparticles with lightly-crosslinked core and hydrophilic surface groups are synthesized by monomer-to-particle direct methodology, characterized, and then used as scaffold polymer/surfactant to produce drug nanoparticles via the emulsion-freeze-drying approach. This method can be used for model organic dye and different poorly water-soluble dye/drugs. Aqueous drug nanocrystals dispersions can be achieved with high ratio of drug to stabilizer and relatively uniformed nanoparticle sizes.However, the emulsion freeze-drying also need low temperature. Therefore, we studied the preparation of poorly water-soluble drug nanoparticles by ambient solvent evaporation from ethanol solutions at room temperature. The resulting dry materials offer excellent nanoparticle stability and easy storage & transportation and can be readily dissolved in water to produce aqueous drug nanoparticles suspensions. The key to the success of this approach is the use of branched block copolymers PEG-PNIPAM which facilitates the formation of drug nanoparticles during solvent evaporation and stabilize the drug nanoparticles in aqueous suspensions. Among the hydrophobic compounds investigated, ketoprofen nanoparticles around 200 nm (stable up to 9 months) can be produced with a nanoparticle yield of 96% at a polymer:drug ratio of 3:1 (or 80% at the ratio of 1:1). There is great potential to apply this method to other hydrophobic drug compounds through rational design and synthesis of branched copolymers.